Water-promoted, silver-phosphine complex-catalyzed stereoselective cyclization of 2-(1-Hydroxy-3-arylprop-2-ynyl)phenols leading to a highly efficient approach to aurones

Article abstract of DOI:10.1080/00397911.2010.517613

Silver-phosphine complexes can be utilized as highly efficient catalysts for the cyclization of 2-(1-hydroxy-3-arylprop-2-ynyl)phenols (1) to give product 2, key intermediates to synthesize aurones (4), with good yields and stereoselectivities in water-to

Full text of DOI:10.1080/00397911.2010.517613

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Water-Promoted, Silver–Phosphine
Complex–Catalyzed Stereoselective
Cyclization of 2-(1-Hydroxy-3-
arylprop-2-ynyl)phenols Leading to a
Highly Efficient Approach to Aurones
Mingdeng Lin a , Min Yu a , Chengyan Han a , Chao-Jun Li b &
Xiaoquan Yao a
a Department of Applied Chemistry, School of Material Science and
Engineering , Nanjing University of Aeronautics and Astronautics ,
Nanjing , P. R. China
b Department of Chemistry , McGill University , Montreal , Canada
Published online: 27 Jul 2011.
To cite this article: Mingdeng Lin , Min Yu , Chengyan Han , Chao-Jun Li & Xiaoquan Yao (2011)
Water-Promoted, Silver–Phosphine Complex–Catalyzed Stereoselective Cyclization of 2-(1-
Hydroxy-3-arylprop-2-ynyl)phenols Leading to a Highly Efficient Approach to Aurones, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:21, 3228-3236, DOI: 10.1080/00397911.2010.517613
To link to this article: http://dx.doi.org/10.1080/00397911.2010.517613
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Synthetic Communications1, 41: 3228–3236, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.517613
WATER-PROMOTED, SILVER–PHOSPHINE COMPLEX–
CATALYZED STEREOSELECTIVE CYCLIZATION OF
2-(1-HYDROXY-3-ARYLPROP-2-YNYL)PHENOLS
LEADING TO A HIGHLY EFFICIENT APPROACH TO
AURONES
Mingdeng Lin,1 Min Yu,1 Chengyan Han,1 Chao-Jun Li,2 and
Xiaoquan Yao1
1Department of Applied Chemistry, School of Material Science and
Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing,
P. R. China
2Department of Chemistry, McGill University, Montreal, Canada
GRAPHICAL ABSTRACT
Abstract Silver–phosphine complexes can be utilized as highly efficient catalysts for the
cyclization of 2-(1-hydroxy-3-arylprop-2-ynyl)phenols (1) to give product 2, key inter-
mediates to synthesize aurones (4), with good yields and stereoselectivities in water–toluene
mixed solvent. With fluoride as the counteranion, complete E- or Z- stereoselectivities were
achieved at high temperature or room temperature, respectively. Furthermore, after remov-
ing water from the reaction mixtures, the toluene solution containing crude products 2 can
be treated by MnO2 directly without further purification, to give aurones 4 in good yields.
Keywords Catalyzed cyclization; silver–phosphine complex; syntheses of aurones;
water-promoted
INTRODUCTION
(Z)-2,3-Dihydrobenzofuran-3-ol derives (2) are key intermediates for the
syntheses of aurones (4), which have exhibited a wide range of biological activities
and have been used as antifungal agents, tyrosinase inhibitors, antioxidants, and
Received December 7, 2009.
Address correspondence to Xiaoquan Yao, Department of Applied Chemistry, School of Material
Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.
E-mail: yaoxq@nuaa.edu.cn
3228

SILVER COMPLEX–CATALYZED CYCLIZATION
3229
others.[1] Wu,[2] Michael,[3] Agrawal,[4] Morimoto,[5] and others reported different
synthetic methods to obtain aurones. Among the reported methods, Pale and his
coworkers recently reported a three-step approach based on a gold(I)-catalyzed
cyclization of 2-(1-hydroxy-3-arylprop-2-ynyl)phenols (1) followed by oxidation of
the cyclized product 2 with MnO2, which led to an efficient and expeditious synthesis
of aurones.[6] However, this procedure has certain disadvantages: The formation of
flavones cannot be completely prevented, the catalyst is relatively expensive and
requires high loading, and usually a long reaction time is required, which sometimes
limits versatility and applicability in industrial processes.
Very recently, we also reported a highly efficient water-triggered, counteranion-
controlled and silver–phosphine complex–catalyzed stereoselective cascade
alkynylation=cyclization of terminal alkynes with salicylaldehydes leading to substi-
tuted 2,3-dihydrobenzofuran-3-ol derivatives (2).[7] In the procedure, various salicy-
laldehydes could be utilized effectively, except for substrates with strong
electron-withdrawing groups; however, long heating times were usually required.
We also noted that water was the best solvent in the reaction, and introduction of
other organic solvents would result in the deactivation of catalyst. To further study
the detailed mechanism of the reaction, compound 1 was synthesized and some sil-
ver(I)–phosphine complexes were evaluated for the annulation of 1. These silver(I)
complexes show high efficiency in catalyzing the cyclization with good yields and
stereoselectivities. A much better functional group compatibility than in the cascade
process was also observed. Furthermore, in contrast to our previously reported
results, the Ag(I)–phosphine complexes show the best activity for the cyclization
in a water–toluene biphasic system with low catalyst loading at room temperature.
RESULTS AND DISCUSSION
4-Bromo-2-(1-hydroxy-3-phenylprop-2-ynyl)phenol (1b) was selected as the
representative substrate to screen the catalysts. Following the conditions described
previously,[7] Cy3PAgCl was examined first in a water–phenylacetylene mixed sol-
vent. After 3 h at 70 ꢀC, a moderate yield of the desired cyclization product was
observed (entry 1, Table 1). Some other organic solvents, instead of phenylacetylene,
were then introduced as cosolvents (entries 2–6). Interestingly, any solvents that are
soluble in water disfavored the reaction (entries 2–4). On the other hand, when
water-insoluble toluene and dichloroethane were used as cosolvents, the catalyst
showed the best activity. Even at room temperature, total conversion of the starting
materials was observed within 1.5–2 h, and ca. 80% yields were achieved with 5 mol%
of catalyst (entries 5 and 6). Compared with the results obtained from the corre-
sponding reaction in pure organic solvents (entries 5 and 6 vs. entries 7–9), the
Ag(I)–phosphine complex–catalyzed cyclization seems to be an on-water reaction,[8]
which tends to proceed at the interface of water and organic solvent. Subsequently,
the ratio of water and toluene was studied, and a 1:1 mixture of water and toluene
gave the best yield (entries 5, 10, and 11). Even with 1 mol% of catalyst, 77% of yield
was still achieved with a prolonged reaction time (entries 12 and 13).
Several kinds of phosphine ligands such as PPh3, n-Bu3P, and Cy3P were also
examined. Among them, both Cy3P and PPh3 gave good results (entry 5 vs. entries
14 and 15). The effect of counteranions on the reaction was then studied with PPh3

3230
M. LIN ET AL.
Table 1. Silver(I)–phosphine complex–catalyzed annulation of 1ba
Entry
Conditions
Resultb (%)
1
2
Cy3PAgCl 10 mol%, water=PhCꢁCH, i-Pr2NEt 20 mol%, 70 ꢀC, 3 h
Cy3PAgCl 5 mol%, water=THF (1:1), i-Pr2NEt 10 mol%, 70 ꢀC, 24 h
Cy3PAgCl 5 mol%, water=CH3CH2OH (1:1), i-Pr2NEt 10 mol%, 70 ꢀC, 24 h
Cy3PAgCl 5 mol%, water=MeCN (1:1), i-Pr2NEt 10 mol%, 70 ꢀC, 24 h
Cy3PAgCl 5 mol%, water=toluene (1:1), i-Pr2NEt 10 mol%, rt, 1.5 h
Cy3PAgCl 5 mol%, water=CH2ClCH2Cl (1:1), i-Pr2NEt 10 mol%, rt, 2 h
Cy3PAgCl 5 mol%, MeCN, i-Pr2NEt 10 mol%, 70 ꢀC, 3 h
71
46
24
33
80
80
22
7
3
4
5
6
7
8
Cy3PAgCl 5 mol%, toluene, i-Pr2NEt 10 mol%, 70 ꢀC, 3 h
9
Cy3PAgCl 5 mol%, CH2ClCH2Cl, i-Pr2NEt 10 mol%, 70 ꢀC, 24 h
Cy3PAgCl 5 mol%, water=toluene (1:4), i-Pr2NEt 10 mol%, rt, 4 h
Cy3PAgCl 5 mol%, water=toluene (4:1), i-Pr2NEt 10 mol%, rt, 1.5 h
Cy3PAgCl 10 mol%, water=toluene (1:1), i-Pr2NEt 10 mol%, rt, 1 h
Cy3PAgCl 1 mol%, water=toluene (1:1), i-Pr2NEt 10 mol%, rt, 9 h
Bu3P=AgCl 5 mol%, water=toluene (1:1), i-Pr2NEt 10 mol%, rt, 5 hc
Ph3PAgCl 5 mol%, water=toluene (1:1), i-Pr2NEt 10 mol%, rt, 1.5 h
Ph3PAgBr 5 mol%, water=toluene (1:1), i-Pr2NEt 10 mol%, rt, 1.5 h
Ph3PAgI 5 mol%, water=toluene (1:1), i-Pr2NEt 10 mol%, rt, 1.5 h
Cy3PAgCl 5 mol%, water=toluene (1:1), i-Pr2NEt 5 mol%, rt, 2.5 h
Cy3PAgCl 5 mol%, water=toluene (1:1), i-Pr2NEt 20 mol%, rt, 1.5 h
Cy3PAgCl 5 mol%, water=toluene (1:1), no base, rt, 24 h
29
81
78
79
77
73
79
57
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
75
79
Trace
78
78
58
27
15
79
Cy3PAgCl 5 mol%, water=toluene (1:1), NaHCO3 10 mol%, rt, 4 h
Cy3PAgCl 5 mol%, water=toluene (1:1), K3PO4 10 mol%, rt, 3 h
Cy3PAgCl 5 mol%, water=toluene (1:1), pyridine 10 mol%, rt, 24 h
Cy3PAgCl 5 mol%, water=toluene (1:1), aniline 10 mol%, rt, 24 h
Cy3PAgCl 5 mol%, water=toluene (1:1), 2,6-lutidine 10 mol%, rt, 24 h
Cy3PAgCl 5 mol%, water=toluene (1:1), i-Pr2NEt 10 mol%, rt, 2. h, in air
a1b (0.15 mmol), Cy3PAgCl (5 mol%), and base (10 mol%), solvent 3 mL, room temperature.
bIsolated yield.
cThe catalyst was prepared in situ by mixing phosphine ligand and AgCl in toluene and stirring for 4 h.
as ligand. Chloride gave the highest yield under similar reaction condition (entries
15–17).
It is worthy noting that a catalytic amount of base is also important in the reac-
tion. Several kinds of organic or inorganic base were studied, and i-Pr2NEt was
found to be the most effective (entries 18–25). As shown in entries 21 and 22, an
inorganic base such as NaHCO3 and K3PO4 also gave good results with a slightly
prolonged reaction time. Furthermore, although air-sensitive phosphine ligands were
used in current studies, no significant decrease in either catalytic activity or yield was
observed even when the reaction was carried out in air (entry 26).
Thus, under the optimized conditions [Cy3PAgCl 5 mol%, i-Pr2NEt 10 mol% in
toluene–water (1:1) mixed solvent], a variety of propargylic alcohol substrates 1, pre-
pared from substituted salicylaldehydes and terminal alkynes, could be utilized in the

SILVER COMPLEX–CATALYZED CYCLIZATION
3231
catalytic reaction to give product 2 in moderate to good yields with high stereoselec-
tivities (Table 2). As shown in Table 2, the substrates bearing electron-withdrawing
groups such as nitro- groups (in 1f and 1g) furnished the cyclization products 2f and
2g in 83% and 79% yields, respectively (entries 6 and 7, Table 2). It is worth mention-
ing that in our previous study on the Ag(I)–phosphine complex–catalyzed cascade
alkynylation=cyclization of terminal alkynes with salicylaldehydes, nitro-substituted
salicylaldehyde 1f could not give the desired products at all, whereas poor yield was
obtained for 1g.[7] On the other hand, when the bulky alkyl group was introduced, no
obvious decrease in yields was observed except a prolonged reaction time was
required (entries 8 and 9), and up to 91% of yield was achieved with 1h as starting
material.
Compared with good functional group compatibility on salicylaldehydes, the
substitutes on alkynes show significant effects on the reaction. As shown by entries
10–14, the electron-donating group on arylacetylene disfavored the reaction: with
Me- and MeO- as the substitutes, only about 70% of yields of the desired products
were observed. In all cases, no other regio- or stereoisomer was observed.
The relationship between the E=Z selectivity and counteranions was also stud-
ied (Table 3). By using AgCl as the catalyst precursor, only Z-isomer was observed
after a long time of stirring at room temperature (entry 1, Table 3). When AgF was
utilized together with Cy3P as ligand, after 24 h of stirring at room temperature, we
Table 2. Cy3PAgCl-catalyzed cyclization of 2a
Entry
Substrate
R1
R2
R3
Conditions
Product
Yieldb (%)
1
2
1a
1b
1c
1d
1e
1f
H
Br
H
H
H
H
rt, 3 h
rt, 1.5 h
rt, 4 h
2a
2b
2c
2d
2e
2f
89
80
83
76
76
83
79
91
88
89
65
67
66
77
3
Br
Cl
Br
H
H
4
H
rt, 2 h
rt, 5 h
5
Cl
Cl
H
H
6
NO2
Cl
H
rt, 1.5 h
rt, 1 h
rt, 6 h
7
1g
1h
1i
NO2
Br
NO2
H
H
2g
2h
2i
8
t-Bu
t-Bu
H
H
9
H
Cl
rt, 7 h
rt, 2 h
rt, 4 h
10
11
12
13
14
1j
2j
1k
1l
H
Br
H
CH3
CH3
-OCH3
-OCH3
2k
2l
H
rt, 45 min
rt, 3 h
rt, 1 h
1m
1n
H
Br
H
2m
2n
H
a1 (0.15 mmol), Cy3PAgCl (5 mol%), i-Pr2NEt (10 mol%), 1.5 mL of H2O, and 1.5 mL of toluene, room
temperature.
bIsolated yield.

3232
M. LIN ET AL.
Table 3. Counteranion and temperature-controlled E=Z-selectivity of the cyclization of 1aa
Entry
Catalyst
Conditions
Yield of 2a:3a (%)b
1
2
3
4
5
Cy3PAgCl (5 mol%)
AgF=Cy3P (1:1)
AgF=Cy3P (1:1)
AgF=Cy3P (1:1)
AgF=Cy3P (1:1)
H2O=toluene, rt, 24 h
H2O=toluene, rt, 24 h
H2O=toluene, 100 ꢀC, 24 h
H2O=CH2Cl2, rt, 24 h
H2O=CH2Cl2, 100 ꢀC, 24 h
85 Only Z
40 (2a:3a ¼ 2:1)
70 (2a:3a ¼ 2:1)
83 Only Z
81 Only E
a1a (0.15 mmol), Cy3P (5 mol%), AgF (5 mol%), i-Pr2NEt (10 mol%), 1.5 mL of H2O, and 1.5 mL of
toluene, room temperature.
bYields were determined by 1H NMR with 0.1 mmol of nitromethane as internal standard.
Scheme 1. The one-pot cyclization-oxidation for aurone synthesis.
noticed the formation of E-isomer 3a with poor overall yield (entry 2); whereas at
100 ꢀC for 24 h, the same ratio of E=Z was observed with 70% yield (entry 3). Sur-
prisingly, when CH2Cl2 was used as cosolvent, the temperature became the switch
for E=Z selectivity: at room temperature, only Z-isomer was obtained, while com-
plete stereoselectivity toward E-isomer was achieved with 83% of yield at 100 ꢀC.
This result suggested that the formation of Z-isomer might be kinetically controlled
and the E-isomer might be thermodynamically controlled.
Toluene=water mixed solvent utilized in the reaction provided a possibility to
carry out a one-pot reaction to prepare aurones (4) directly without additional puri-
fication for compound 2. After removing water from the reaction mixture by pipette,
the crude product 2b was oxidized effectively by adding MnO2 directly to the toluene
solution, and up to 81% of total yield of aurone 4b was obtained (Scheme 1).
CONCLUSION
In summary, silver–phosphine complexes can be used as highly efficient
catalysts for the cyclization of 2-(1-hydroxy-3-arylprop-2-ynyl)phenols (1) in water–
toluene mixed solvent at room temperature. In the reaction, both water and phos-
phine ligands are the key factors to activate the catalyst. A variety of substrates 1

SILVER COMPLEX–CATALYZED CYCLIZATION
3233
could be utilized in the catalytic reaction to give product 2 in moderate to good yields
and high stereoselectivities. Furthermore, by removing water from the reaction mix-
tures, the toluene solution containing crude product 2 could be treated by MnO2
directly without further purification to give aurone 4 in good yields. The procedure
provides an alterative method to synthesize aurones with high efficiency and high
stereoselectivities.
EXPERIMENTAL
All experiments were carried out under an inert atmosphere of nitrogen. Flash
column chromatography was performed over silica gel 30–60 mm. 1H NMR and 13
C
NMR spectra were acquired by 400 MHz and 100 MHz, or 300 MHz and 75 MHz,
respectively, and referenced to the internal solvent signals. High-resolution mass
spectra (HRMS) were measured at the Shanghai Institute of Organic Chemistry,
CAS. The data for all products are described.
Typical Reaction Procedure 1 (Entry 1 in Table 2)
2-(1-Hydroxy-3-phenylprop-2-ynyl)phenol (1a, 0.15 mmol), Cy3PAgCl (3.2 mg,
0.0075 mmol, 5 mol%), and 2.6 mL of i-Pr2NEt (0.015 mmol, 10 mol%) were added
into a 10-mL Schlenk tube with 1.5 mL of toluene and 1.5 mL of distilled water
under nitrogen. The mixture was stirred at room temperature for 3 h. The reaction
was stopped and extracted with ether (3 ꢂ 3 mL). The combined organic phase was
dried with Na2SO4 and concentrated under reduced pressure. The residue was pur-
ified by flash column chromatography on silica gel (eluent 20:1 hexanes and ethyl
acetate). Compound 2a was obtained in 80% yield.
Typical Procedure 2 (Scheme 1)
Following the procedure described in Typical Procedure 1, 2 mmol of
2-(1-hydroxy-3-phenylprop-2-ynyl)phenol (1b) was added into a mixed solvent of
water (5 mL) and toluene (5 mL) in the presence of Cy3PAgCl (42.2 mg, 0.1 mmol,
5 mol%) and 34 mL of i-Pr2NEt (0.2 mmol, 10 mol%). When the reaction was over,
the aqueous layer was removed by pipette. The toluene solution was then cooled
in an ice bath, and MnO2 (6 mmol) was added. The mixture was stirred at room tem-
perature for 4 h and then filtered through celite. The solution was concentrated under
reduced pressure, and the residue was purified by flash column chromatography on
silica gel (eluent: hexanes=EtOAc 40:1). Compound 4b was obtained in 81% yield.
Selected Data
(Z)-2-Benzylidene-2,3-dihydrobenzofuran-3-ol (2a).[7] IR (KBr): nmax
1
3414, 1683, 1612, 1601, 1479, 1290, 1236, 1088, 1022, 908 cmꢃ1; H NMR (CDCl3,
400 MHz, ppm) d 7.74 (d, J ¼ 7.9 Hz, 2H), 7.50 (d, J ¼ 7.2 Hz, 1H), 7.42–7.34 (m,
3H), 7.28–7.24 (m, 1H), 7.12–7.09 (m, 2H), 6.02 (s, 1H), 5.76 (d, J ¼ 12 Hz, 1H),
2.32 (d, J ¼ 12 Hz, 1H); 13C NMR (CDCl3, 100 MHz, ppm) d 157.8, 157.0, 134.5,
130.6, 128.7, 128.5, 126.9, 126.8, 125.7, 122.9, 110.7, 106.0, 72.5.

3234
M. LIN ET AL.
(Z)-2-Benzylidene-5-bromo-2,3-dihydrobenzofuran-3-ol
(2b).[7] IR
(KBr): nmax 3434, 3058, 1644, 1608, 1470, 1236, 1097, 1005, 907 cmꢃ1; H NMR
(CDCl3, 400 MHz, ppm) d 7.70 (d, J ¼ 7.8 Hz, 2H), 7.62 (s, 1H), 7.46 (dd, J ¼ 1.2,
5.3 Hz, 1H), 7.40 (t, J ¼ 8.1 Hz, 2H), 7.27 (dd, J ¼ 5.2, 8.2 Hz, 1H), 6.99 (d,
J ¼ 8.5 Hz, 1H), 6.03 (s, 1H), 5.77 (d, J ¼ 6.6 Hz, 1H), 2.24 (d, J ¼ 7.9 Hz, 1H); 13C
NMR (CDCl3, 100 MHz, ppm) d 156.7, 156.5, 134.0, 133.5, 129.2, 128.5, 127.1,
115.0, 112.3, 106.6, 72.2.
1
(Z)-2-Benzylidene-5,7-dibromo-2,3-dihydrobenzofuran-3-ol (2c).[7] IR
(KBr): nmax 3435, 3062, 1690, 1600, 1492, 1450, 1228, 1174, 1113, 1075, 1005,
1
903 cmꢃ1; H NMR (CDCl3, 400 MHz, ppm) d 7.75 (d, J ¼ 7.7 Hz, 2H), 7.66 (d,
J ¼ 1.6 Hz, 1H), 7.56 (d, J ¼ 0.9 Hz, 1H), 7.42 (t, J ¼ 7.5 Hz, 2H), 7.30 (m, 1H),
6.07 (s, 1H), 5.84 (d, J ¼ 8.4 Hz, 1H), 2.29 (d, J ¼ 9.2 Hz, 1H); 13C NMR (CDCl3,
100 MHz, ppm) d 155.2, 154.5, 135.7, 133.6, 129.9, 129.0, 128.6, 127.7, 127.4,
115.2, 107.8, 104.3, 72.9.
(Z)-2-Benzylidene-5-chloro-2,3-dihydrobenzofuran-3-ol
(2d).[7] IR
(KBr): nmax 3425, 3054, 2923, 1690, 1611, 1475, 1237, 1100, 1022, 908 cmꢃ1; H
NMR (CDCl3, 400 MHz, ppm) d 7.71 (d, J ¼ 7.6 Hz, 2H), 7.49 (s, 1H), 7.41 (t,
J ¼ 7.6 Hz, 2H), 7.33–7.25 (m, 2H), 7.04 (d, J ¼ 8.6 Hz, 1H), 6.04 (s, 1H), 5.78 (s,
1H), 2.20 (bs, 1H); 13C NMR (CDCl3, 100 MHz, ppm) d 156.6, 156.2, 134.1,
130.6, 128.7, 128.6, 128.5, 127.9, 127.1, 125.9, 111.8, 106.6, 72.3.
1
(Z)-2-Benzylidene-5,7-dichloro-2,3-dihydrobenzofuran-3-ol (2e).[7] IR
1
(KBr): nmax 3350, 3068, 1687, 1605, 1462, 1229, 1186, 1117, 1017, 902 cmꢃ1; H
NMR (CDCl3, 400 MHz, ppm) d 7.74 (d, J ¼ 7.6 Hz, 2H), 7.44–7.37 (m, 4H), 7.30
(d, J ¼ 7.4 Hz, 1H), 6.08 (s, 1H), 5.82 (d, J ¼ 9.0 Hz, 1H), 2.28 (d, J ¼ 9.5 Hz, 1H);
13C NMR (CDCl3, 100 MHz, ppm) d 156.7, 156.5, 134.1, 133.5, 129.2, 128.8,
128.7, 128.5, 127.1, 115.0, 112.3, 106.6, 72.2.
(Z)-2-Benzylidene-7-nitro-2,3-dihydrobenzofuran-3-ol (2f).[6] IR (KBr):
1
nmax 3288, 2927, 1601, 1520, 1471, 1338 cmꢃ1; H NMR (CDCl3, 400 MHz, ppm)
d 8.42 (s, 1H), 8.32 (d, J ¼ 8.9 Hz, 1H), 7.71 (d, J ¼ 7.7 Hz, 2H), 7.42 (t, J ¼ 7.5 Hz,
2H), 7.32 (d, J ¼ 7.3 Hz, 1H), 7.20 (d, J ¼ 8.9 Hz, 1H), 6.14 (s, 1H), 5.87 (d,
J ¼ 9.0 Hz, 1H), 2.48 (d, J ¼ 9.1 Hz, 1H); 13C NMR (CDCl3, 100 MHz, ppm) d
162.1, 156.0, 143.7, 133.5, 129.0, 128.7, 128.4, 127.7, 127.5, 122.3, 111.0, 108.5, 71.4.
(Z)-2-Benzylidene-5-chloro-7-nitro-2,3-dihydrobenzofuran-3-ol (2g).[7]
IR (KBr): nmax 3537, 3100, 1693, 1625, 1597, 1527, 1449, 1350, 1220, 1199, 1126,
1
1050, 866, 760 cmꢃ1; H NMR (d6-DMSO, 400 MHz, ppm) d 8.16 (s, 1H), 7.92 (s,
1H), 7.81 (d, J ¼ 7.4 Hz, 2H), 7.42 (dd, J ¼ 7.3, 7.3 Hz, 2H), 7.28 (t, J ¼ 7.0 Hz,
1
1H), 6.14 (s, 1H), 5.82 (s, 1H; H NMR (CDCl3, 400 MHz, ppm) d 8.14 (s, 1H),
7.83 (d, J ¼ 7.6 Hz, 2H), 7.77 (s, 1H), 7.44 (dd, J ¼ 7.5, 7.5 Hz, 2H), 7.33 (t,
J ¼ 7.5 Hz, 1H), 6.17 (s, 1H), 5.86 (s, 1H), 2.40 (bs, 1H); 13C NMR (d6-DMSO,
100 MHz, ppm) d 157.1, 150.2, 135.6, 134.04, 132.63, 132.56, 129.1, 129.0, 127.8,
126.9, 125.0, 107.3, 69.6.
(Z)-2-Benzylidene-7-bromo-5-tert-butyl-2,3-dihydrobenzofuran-3-ol (2h).[7]
IR (KBr): nmax 3408, 2963, 2868, 1692, 1613, 1479, 1234, 1122, 1087, 1030,
1
911 cmꢃ1; H NMR (CDCl3, 400 MHz, ppm) d 7.78 (d, J ¼ 7.8 Hz, 2H), 7.51 (d,

SILVER COMPLEX–CATALYZED CYCLIZATION
3235
J ¼ 1.6, 1H), 7.48 (d, J ¼ 0.7 Hz, 1H), 7.42 (t, J ¼ 7.6 Hz, 2H), 7.28 (m, 1H), 6.06 (s,
1H), 5.84 (d, J ¼ 9.3 Hz, 1H), 2.20 (d, J ¼ 9.7 Hz, 1H), 1.35 (s, 9H); 13C NMR
(CDCl3, 100 MHz, ppm) d 156.3, 153.0, 148.1, 134.1, 130.7, 128.9, 128.6, 127.9,
127.0, 121.5, 106.9, 102.7, 73.5, 34.8, 31.5.
(Z)-2-Benzylidene-7-nitro-5-tert-butyl-2,3-dihydrobenzofuran-3-ol (2i).
IR (KBr): nmax 3515, 2960, 2870, 1633, 1542, 1327, 1224, 1096, 1040, 895 cmꢃ1
;
1H NMR (CDCl3, 400 MHz, ppm) d 8.16 (s, 1H), 7.86–7.85 (m, 3H), 7.44 (t,
J ¼ 7.4 Hz, 2H), 7.32–7.27 (m, 1H), 6.15 (s, 1H), 5.84 (d, J ¼ 9.0 Hz, 1H), 2.34 (d,
J ¼ 9.5 Hz, 1H), 1.39 (s, 9H); 13C NMR (CDCl3, 100 MHz, ppm) d 155.8, 149.8,
147.2, 133.4, 132.2, 129.3, 129.1, 128.8, 127.7, 122.8, 108.7, 71.4, 35.0; GC=MS
m=z (%) 325 (Mþ, 100), 324, 308, 278, 248, 206, 188, 132, 105, 77; HRMS calcd.
for C19H19NO4: 325.1314; found: 325.1316.
(Z)-2-(4-Chlorobenzylidene)-2,3-dihydrobenzofuran-3-ol
(2j).[7] IR
(KBr): nmax 3331, 2923, 1684, 1615, 1600, 1466, 1292, 1237, 1134, 1085, 1018,
910 cmꢃ1; 1H NMR (400 MHz, CDCl3) d 7.67 (d, J ¼ 8.5 Hz, 2H), 7.52 (d, J ¼ 7.2 Hz,
1H), 7.37–7.35 (m, 3H), 7.12 (t, J ¼ 7.6 Hz, 2H), 5.98 (s, 1H), 5.78 (d, J ¼ 6.9 Hz, 1H),
2.21 (d, J ¼ 8.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) 157.6, 157.5, 133.1, 132.4,
130.8, 130.0, 128.7, 125.7, 123.1, 110.7, 104.9, 72.6.
Z)-2-(4-Methylbenzylidene)-2,3-dihydrobenzofuran-3-ol
(2k).[7] IR
(KBr): nmax 3387, 3052, 2921, 1688, 1603, 1479, 1467, 1291, 1234, 1134, 1132,
1085, 1010, 906 cmꢃ1
;
1H NMR (CDCl3, 400 MHz, ppm) d 7.64 (d, J ¼ 8.1 Hz,
2H), 7.51 (d, J ¼ 7.2, 1H), 7.36 (dd, J ¼ 0.9, 7.6 Hz, 1H), 7.21 (d, J ¼ 7.9 Hz, 2H),
7.12–7.08 (m, 2H), 6.00 (s, 1H), 5.76 (bs, 1H), 2.39 (s, 3H), 2.20 (bs, 1H); 13C
NMR (CDCl3, 100 MHz, ppm) d 157.8, 156.3, 136.7, 131.7, 130.6, 129.2, 128.6,
127.0, 125.7, 122.8, 110.6, 106.0, 72.5, 21.3.
(Z)-5-Bromo-2-(4-methylbenzylidene)-2,3-dihydrobenzofuran-3-ol (2 l).[7]
IR (KBr): nmax 3423, 3027, 1689, 1607, 1512, 1471, 1236, 1096, 1005, 906 cmꢃ1; 1H
NMR (CDCl3, 400 MHz, ppm) d 7.61–7.58 (m, 3H), 7.46 (dd, J ¼ 1.6, 8.5 Hz, 1H),
7.20 (d, J ¼ 7.9 Hz, 2H), 6.98 (d, J ¼ 8.5 Hz, 1H), 6.00 (s, 1H), 5.74 (s, 1H), 2.38 (s,
3H), 2.24 (bs, 1H); 13C NMR (CDCl3, 100 MHz, ppm) d 156.8, 155.8, 137.0, 133.4,
131.2, 129.2, 128.8, 128.7, 114.8, 112.3, 106.6, 72.2, 21.3.
(Z)-2-(4-Methoxybenzylidene)-2,3-dihydrobenzofuran-3-ol (2m)[6]. IR
(KBr): nmax 3369, 3043, 2997, 2929, 2837, 1685, 1607, 1514, 1462, 1294, 1253,
1
1179, 1130, 1084 cmꢃ1; H NMR (CDCl3, 300 MHz, ppm) d 7.66 (d, J ¼ 8.7 Hz,
2H), 7.49 (d, J ¼ 7.2 Hz, 1H), 7.33 (t, J ¼ 7.8 Hz, 1H), 7.11–7.06 (m, 2H), 6.92 (d,
J ¼ 8.7 Hz, 1H), 5.95 (bs, 1H), 5.74 (d, J ¼ 9.3 Hz, 1H), 3.83 (s, 3H), 2.18 (d,
J ¼ 9.3 Hz, 1H); 13C NMR (CDCl3, 75 MHz, ppm) d 158.6, 157.9, 155.5, 130.7,
130.1, 127.5, 127.2, 125.8, 122.9, 114.1, 110.7, 105.8, 72.6, 55.4.
(Z)-5-Bromo-2-(4-methoxybenzylidene)-2,3-dihydrobenzofuran-3-ol (2n).
IR (KBr): nmax 3354, 3080, 2957, 2836, 1604, 1512, 1471, 1253, 1180, 1095, 1024,
1
904 cmꢃ1; H NMR (CDCl3, 300 MHz, ppm) d 7.64–7.59 (m, 2H), 7.45–7.414 (m,
2H), 6.96–6.89 (m, 2H), 5.95 (s, 1H), 5.72 (d, J ¼ 9.0 Hz, 1H), 3.83 (s, 3H), 2.31
(d, J ¼ 9.6 Hz, 1H); 13C NMR (CDCl3, 75 MHz, ppm) d 158.8, 157.0, 155.0, 133.5,
130.2, 129.5, 129.0, 127.0, 114.9, 114.2, 112.4, 106.4, 72.2, 55.4; MS (EI) m=z (%)

3236
M. LIN ET AL.
330 (100, Mþ ꢃ 2), 315, 301, 287, 236, 152, 132, 117, 89; HRMS calcd. for
C16H11O3Br (M ꢃ 2H): 329.9893; found: 329.9892.
(E)-2-Benzylidene-2,3-dihydrobenzofuran-3-ol (3a).[7] IR (neat, NaCl):
nmax 3332, 2977, 2920, 1600, 1493, 1452, 1378, 1321, 1298, 1253, 1170, 1126, 1079,
1
1041, 945, 885, 843, 802, 775, 742, 698, 537 cmꢃ1; H NMR (CDCl3, 400 MHz,
ppm) d 7.54–7.36 (m, 7H), 7.28–7.22 (m, 2H), 6.53 (s, 1H), 5.94 (b, 1H), 2.77 (b,
1H); 13C NMR (CDCl3, 75 MHz, ppm) d 158.7, 155.3, 140.5, 128.9, 128.6, 128.3,
127.1, 124.6, 123.1, 121.4, 111.6, 104.3, 70.9.
(Z)-2-Benzylidene-5-bromobenzofuran-3(2h)-one (4b).[6] IR (KBr): nmax
1
3081, 1706, 1642, 1600, 1456, 1265, 1176, 1133, 959, 923 cmꢃ1; H NMR (CDCl3,
400 MHz, ppm) d 7.94–7.92 (m, 3H), 7.77 (d, J ¼ 8.7 Hz, 1H), 7.51–7.42 (m, 3H),
7.27 (d, J ¼ 7.1 Hz, 1H), 6.94 (s, 1H);13C NMR (CDCl3, 100 MHz, ppm) d 183.3,
164.7, 146.8, 139.4, 132.0, 131.7, 130.3, 129.0, 127.4, 123.4, 116.4, 114.7, 114.2.
ACKNOWLEDGMENTS
We are grateful for the financial support from the National Natural Science
Foundation of China (20602018 to X. Y.), Natural Science Foundation of Jiangsu
Province (BK2008386 to X. Y.), and NUAA Research Funding (No. 2010169 to
X. Y.).
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